Phospholipase A2S (PLA2S) are essential in the proliferation and differentiation of human epidermis. Strong evidence supports their roles in regulating skin eicosanoid production, formation of the permeability barrier, protection from bacterial invasion, and wound healing. Despite their abundance and very robust activity compared with that of other cell types, PLA2s are only partially characterized in human keratinocytes. We have observed that human primary keratinocytes grown at low densities have a dramatic increase in both arachidonic and linoleic acid release compared to confluent keratinocytes. This cell morphology is correlated with a substantial number of cellular processes. The small monomeric G protein rac has an important role in process formation in other cell types. We hypothesize that a kertinocyte PLA2 is activated by the small monomeric G protein rac and that the coordinated activities of rac and PLA2 cause actin rearrangement necessary for keratinocyte process formation and migration in wound beds. Knowledge about PLA2 activity and identification of the types of PLA2, in human keratinocytes will provide a better understanding of their multifunctional roles in skin and could potentially lead to the development of agents that would improve wound healing and host defense.